The Peoples Republic of China has the second highest overall case burden of TB in the world (behind India). The WHO Global Tuberculosis Report 2013 estimated that, in 2012, China had 1,400,000 cases of TB, with a prevalence of 99/100,000 population and an incidence of 73/100,000 population. For MDR TB, China has the 2nd highest annual number of cases in the world. Among all new TB cases in 2012, an estimated 5.7% (49,000 people) were MDR-TB. Among retreated TB cases in 2012, an estimated 26% (11,000 people) were MDR. Henan Province is Chinas largest province by population, with about 100 million people. By global population rankings, that would make it the 12th largest country in the world, behind Mexico. About ten percent of all new pulmonary TB cases in China each year occur in Henan Province and reported MDR TB rates in Henan are among the highest across the country. In partnership with provincial health authorities in Zhengzhou, the capital of Henan Province, the Tuberculosis Research Section is developing the sites capacity to conduct high-quality clinical research. In 2009, NIAID Deputy Director Hugh Auchincloss signed an Implementing Arrangement with the Henan Provincial Bureau of Health to establish a collaborative research center. In response the provincial government announced that they would construct a new provincial-level infectious diseases hospital to house the research facility and better accommodate the heavy burden of patients in Henan Province. A prospective, longitudinal natural history study entitled A Natural History Study of Tuberculosis in China: Correlates of a Successful Response in Treatment (NIAID 10-I-N060) was approved by the NIAID IRB and enrollment commenced after lab renovation and installation of equipment in March 2010. This protocol enrolled 150 subjects with suspected TB at the Henan Provincial Chest Hospital. The subjects were divided into three cohorts according to suspected diagnosis: A) Acid-fast bacilli (AFB) smear positive pulmonary tuberculosis, B) AFB smear negative pulmonary tuberculosis, and C) extrapulmonary tuberculosis (EPTB). These subjects were actively followed for six months during their initial response to antituberculous chemotherapy, then passively followed for another year, with a phone call at the end of that year to determine TB cure vs. relapse status. Forty-five (45) healthy controls (Cohort D) were also enrolled to determine baseline values for immunologic responses and laboratory values. This study analyzed changes in total volume of disease as assessed by quantitative CT scanning at baseline, 2, and 6 months. In addition, we monitored chemotherapeutic regimens, changes in the host immune response, overall changes in clinical parameters, initial and acquired drug-resistance of the infecting isolates, and changes in bacterial and host markers in subject samples during chemotherapy. In each case, we looked for associations of these parameters with rates of disease resolution correlated with specific structural features determined by CT scanning at the site of TB disease. This study will allow us to evaluate eligibility criteria for future clinical trials, establish TB diagnostic accuracy, understand the local standard of care, initial anti-TB regimen selection and subsequent modifications, evaluate mycobacterial strain characteristics, extent of disease, types of lesions and host immunologic response to chemotherapy, as well as identify surrogate markers to monitor the response to chemotherapy. As of August 1, 2014, all 150 subjects were fully enrolled into the study with follow-up phone calls one year later (18 months after enrollment) to ascertain TB cure vs. relapse status also completed. Study personnel cultured bacteria from sputa and other samples, collected and froze plasma, performed gamma interferon stimulation assays, and completed case report forms on a regular basis. The OpenClinica database designed for the study is being used by the data entry personal, allowing us to monitor the progress of the study remotely. The study team completed QuantiFERON (QFT) testing and two molecular tests for establishing drug resistance. The QFT test uses whole blood to detect interferon gamma production in response to mycobacterial antigens in serial samples collected prior to and during anti-tubercular treatment. We also assessed the changes in cytokine and chemokine levels in the subjects sera during treatment in collaboration with Drs Katrin Mayer-Barberplan and Dr Alan Sher. In addition, bacterial DNA was isolated from cultured sputa and/or sputum sediment and was used to detect rifampicin and isoniazid resistance (Hain test) and speciate non-tuberculous mycobacteria (NTM) (reverse line blot assay). Among the subject specimens, 11/76 (14.5%) were determined to be multidrug resistant by culture, 3/76 (3.9%) had XDR TB and 3/79 (3.8%) contained predominantly NTM based on the Reba results. Two of the 3 NTMs were identified as M. intracellulare and both were from subjects with a history of TB treatment. While the rate of MDR TB appears lower than might be expected in a tertiary hospital, 80% of subjects enrolled in the study were never previously treated for TB. In addition, most patients admitted to the hospital were not eligible to enroll in this study due to the inclusion criterion of no more than 14 days of TB treatment before enrollment. Half of the confirmed MDR TB cases occurred in subjects who were treatment nave, suggesting on-going primary transmission of MDR TB in this study population. In FY2014, a new study initiated at this site, titled Feasibility and accuracy of a novel Xpert cartridge for rapid molecular detection of drug resistant Mycobacterium tuberculosis in sputum (DMID Protocol Number 13-0029; DMID Funding Mechanism: Award Number N01AI90500C). This study is being conducted in conjunction with Susan Dorman at Johns Hopkins University under a grant from DMID. The primary objective of this prospective, cross-sectional study is to estimate the sensitivity and specificity of the investigational Xpert cartridge for detection of M. tuberculosis resistance to isoniazid, fluoroquinolones, and aminoglycosides. 550 subjects will be enrolled in Zhengzhou, Henan Province and Seoul, South Korea. The study began enrollment on June 5, 2014 and, as of July 25, 2014, 77 subjects had been enrolled, which is above the target enrollment for that date (target of 55 subjects). The China site had enrolled 50 participants, above their target enrollment for that date (target of 32 subjects). The study is progressing smoothly thus far and is expected to last about 12 months.